Portugal, past and present

The early days

Crystallography was taught in the early thirties as an independent discipline at the Geology Departments, Faculty of Sciences of Porto and Lisbon Universities. The didactic book “Cristalografia” published in 1942 by Domingos Rosas da Silva from Porto was a reference and teaching tool for decades. In 1980, “Elementos de Cristalografia” by Frederico Sodré Borges (also from Porto) expanded the topics covered by the previous book, introducing chapters on X-ray Crystallography and physical properties of crystals.

The first applications of X-ray crystallography appeared in Coimbra in 1923, as part of the PhD thesis of José Custódio de Morais.

In 1930, a brilliant graduate student of the Physics Department, João R. de Almeida Santos, was awarded a research grant to work at the Physics Laboratory of Manchester University, UK, on X-ray determination of crystal structures, under the supervision of Sir Lawrence Bragg. In January 1935 he obtained his PhD with a thesis entitled “The Structure of Anhydrous Cobaltous Chloride, CoCl₂, at Room and Very Low Temperatures; Cæsium, Rubidium and Thallium Salts of Certain 12-Heteropoly Acids”. On his return to Coimbra, Almeida Santos trained another research student, Luiz Vaz de Sampayo, who then had the opportunity to work at University College in London, from 1951 to 1953, under the supervision of Dame Kathleen Lonsdale. This pioneering work certainly constituted the embryo of the present X-Ray Diffraction Center in Coimbra.

In Lisbon, Professor of Mineralogy Carlos Torres de Assunção developed the identification of minerals by X-ray powder diffraction, and in co-authorship with Julio Garrido from Madrid, the first edition of “Tables pour la determination des minéraux au moyen des rayons X” was published in 1952 by the Laboratory of Mineralogy and Geology, Lisbon Faculty of Sciences. This mineralogical trend was pursued by a research student, José Lima-de-Faria, under the supervision of Peter Gay at the University of Cambridge, UK. Part of that work was published in 1964 by the Junta de Investigações do Ultramar as volume 112 of the series “Estudos, Ensaios & Documentos”, entitled “Identification of Metamict Minerals by X-ray Powder Photographs” which became one of the most quoted reference works in the metamict minerals field.

In 1964, a small research group in Coimbra led by Luis Alte da Veiga, began investigations of the crystal structures of metals and alloys, in particular those of Cr₃Si and related intermetallic compounds. The scope of this research grew rapidly, progressing towards interdisciplinary research topics using a variety of X-ray and neutron diffraction techniques.

Since then, many centres have emerged throughout the country in new areas of research. The following chapters in this article describe current research topics, organized by scientific fields.

The present

Physics and Crystallography: At the X-ray Diffraction Centre for Materials Research (CEMDRX) (Physics Department, Coimbra University), single crystal X-ray diffraction is used to obtain accurate measurements of electron density distributions in crystalline solids. The results are compared with state of the art ab-initio calculations using density functional or LCAO-HF methods ^[1a]. Synchrotron radiation scattering studies of magnetic and electronic properties of solids are performed by members of CEMDRX at the ESRF in Grenoble. In particular, the novel technique of Resonant X-ray Magnetic Scattering, which combines diffraction and spectroscopy, is used to investigate the magnetic and electronic structure of lanthanide and actinide compounds ^[1a,].

References

[1a] University of Coimbra, Physics Dept., CEMDRX, Margarida Costa (guida@pollux.fi s.uc.pt), Maria José Almeida (ze@pollux.fis.uc.pt), José António Paixão (jap@pollux.fi s.uc.pt), Ana Matos Beja (ana@pollux.fi s.uc.pt), Manuela Ramos Silva (manuela@pollux.fi s.uc.pt).
[1b] University of Coimbra, Physics Dept., CEMDRX, Lourdes Andrade (lourdes@pollux.fi s.uc.pt)

Mineralogical Crystallography and Crystal Chemistry: Since the establishment of nomenclature for crystal structure types and their classification by José Limade-Faria and Maria Ondina Figueiredo in the Seventies, Crystal Chemistry has been developed at the Crystallography and Mineralogy Centre (CCM) of the Tropical Research Institute (IICT) in Lisbon along two lines.

A successful 2D+1D way of representing closest-packed structural arrangements (condensed models) of crystal structures invented by J. Lima-de-Faria in the sixties was extended to the analysis of loose atomic packings, complex intermetallics and silicates (pyroxenes, amphiboles, micas and feldspars), thereby encompassing an extensive domain of thousands of structures. In parallel, new software was developed for automatic plotting of such condensed crystal structure representations.

The elucidation of structural relationships between minerals and their structural classification, culminating in 1994 with the publication of “Structural Mineralogy; an Introduction”, was followed by a series of three volumes on the structural classification of minerals (J. Lima-de-Faria, Kluwer Academic Publishers, 2001-2004).

Recently, these structural insights are being used to develop models for innovative applications, reviewing nanomineralogy from a crystallographic perspective^[1].

The identification of copper minerals used to produce color variation in ancient glasses and glazes illustrates the powers of spectroscopic techniques based on the absorption of either soft or hard X-rays at synchrotron facilities.

References

[1] CCM-IICT - Crystallography and Mineralogy Centre, Tropical Scientific Research Institute, Maria Ondina Figueiredo (mof@fct.unl.pt), Teresa Pereira da Silva (teresa.pena@ineti.pt).

Materials science: Symmetry theory, mathematical crystallography and advanced experimental techniques for structural analysis are being combined by researchers at CCM in Lisbon ^[1] to study less ordered systems. Researchers from the Geophysics Centre of Évora University ^[2] and CENIMAT (Materials Science Centre, Universidade Nova de Lisboa) ^[3] are collaborating in the study of the electronic structure of solids.

The Lisbon group is also examining the crystal chemistry of natural nanophases found in regoliths from semi-arid regions, terrestrial analogues of Martian red soils and synthetic dispersed metal nanoclusters in glasses.

In the Physics Department of Aveiro University [4], the epitaxial growth of crystalline thin films on commercial crystalline structures is analyzed by physical vapour deposition (PVD) and sputtering techniques. Thin films of epitaxial manganite prepared by laser ablation on several oxide substrates are studied by triple axis XRD to determine lattice parameters, misfit and orientation tilting. Crystallographic studies are complemented by real space techniques and emission channelling using radioactive isotopes. XRD analysis of light emitting epitaxial heterostructures includes symmetric and asymmetric reciprocal space mapping, in-plane diffraction and X-ray reflectometry.

The focus of residual stress analysis of textures in the Physics Department of Coimbra University ^[5] is: (i) improvement of experimental techniques for residual stress evaluation, enabling their use in new engineering applications; (ii) analysis of industrial techniques used in manufacturing, control and optimisation of processes; and (iii) modelling and numerical simulation of residual stresses.

At the European synchrotron facility, investigators from CENIMAT, New University of Lisbon ^[3], are using X-ray microtomography to study particle distribution in SiC particle-reinforced functionally graded aluminium composites and Ni-Ti shape memory alloys (SMA).

References

[1] CCM-IICT - Crystallography and Mineralogy Centre, Tropical Scientific Research Institute, Maria Ondina Figueiredo (mof@fct.unl.pt), Teresa Pereira da Silva (teresa.pena@ineti.pt).
[2] Évora University, CGE – Geophysics Centre, José Mirão (jmirao@uevora.pt).
[3] New University of Lisbon, Faculty of Sciences and Technology, CENIMAT – Materials Research Centre, Maria Ondina Figueiredo (mof@fct.unl.pt), Francisco Braz Fernandes (fbf@fct.unl.pt), João Pedro Veiga (jpv@fct.unl.pt).
[4] University of Aveiro, CICECO – Research Centre in Ceramic Materials and Composites, João Rocha (rocha@dq.ua.pt).
[5] University of Coimbra, Physics Dept., CEMDRX, António Morão Dias (morao.dias@dem.uc.pt), António Castanhola Batista (castanhola@ci.uc.pt), José Carlos Prata Pina (zepina@ci.uc.pt) João Paulo Nobre (joão.nobre@dem.uc.pt).

Neutron diffraction: A neutron reactor has been dedicated to physics research in Portugal since the early fifties and neutron diffraction instrumentation at the facility will soon be available to the crystallographic community as well.

However, members of the CEMDRX (Coimbra University) have been already been using European neutron facilities for at least two decades to conduct single crystal neutron diffraction studies of electron density in magnetic materials such as lanthanide and actinide intermetallics^[1,2], oxides^[1] and heavy-fermion^[1-2] compounds. Elastic and inelastic scattering techniques are used to obtain information on static and dynamic properties. Such studies have more recently been extended and/or complemented using synchrotron radiation).

References

[1] University of Coimbra, Physics Dept., CEMDRX, Margarida Costa (guida@pollux.fis.uc.pt), Maria José Almeida (ze@pollux.fi s.uc.pt), José António Paixão (jap@pollux.fis.uc.pt), Lourdes Andrade (lourdes@pollux.fi s.uc.pt), Ana Matos Beja (ana@pollux.fi s.uc.pt), Manuela Ramos Silva (manuela@pollux.fi s.uc.pt).
[2] Instituto Tecnológico e Nuclear, Chemistry Dept., António Pereira Gonçalves (apg@itn.pt), Manuel Almeida (malmeida@itn.pt), Laura Pereira (lpereira@itn.pt), João Carlos Waerenborgh (jcarlos@itn.pt)

Small molecule crystallography: Maria Arménia Carrondo initiated X-ray diffraction studies on organometallic and coordination compounds in Lisbon in 1979. The first automatic four-circle diffractometer was installed in Coimbra in 1981 while Lisbon got its first one in 1986 at ITN (Instituto Tecnológico e Nuclear). A rotating anode arrived at IST (Instituto Superior Técnico) in 1990 and the first CCD was installed at IST in December, 2005. Shared use of these instruments by the two Institutions has led to the solution of 120 structures per year as part of research projects on synthetic organic, inorganic and organometallic chemistry, catalysis, materials and ionic liquids. In Lisbon at Centro de Química Estrutural (CQE-IST) ^[1], and at the Chemistry Department of ITN ^[2], molecular and crystal structure determination focus on structure-property and structure-activity/reactivity relationships of organic semi-conductors, a wide range of organic and planar coordination based molecules, and molecular magnets. New X-ray studies, structural databases and theoretical calculations are combined to determine structure-activity relationships in compounds exhibiting high hyperpolarizabilities, homogeneous catalysts for the polymerization of α-olefins and vanadium compounds having insulin-enhancing and anticancer activities. Other areas of investigation include pharmacophores, polymorphism using co-crystallizations and characterization of ionic liquids.

At ITQB (Instituto de Tecnologia Química e Biológica) ^[3] crystal structure determination focus on organic compounds with chiral properties, new organometallic complexes and the structural characterization of ionic liquid compounds synthetised at ITQB.
At IBMC (Instituto de Biologia Molecular e Celular) and ICBAS (Instituto de Ciências Biomédicas de Abel Salazar) ^[4] xanthone derivatives, triterpenes and diterpenoids with medicinal use are being extracted from plants and marine sponges and characterized. The coordination around the metallic center of copper and nickel complexes is being correlated with dissociation enthalpies.
At CICECO (Research Centre for Ceramics and Composites, Chemistry Department of Aveiro University) ^[5] synthesis and molecular design of new macrocyclic receptors for the selective binding of organic substrates and toxic metals is being guided by molecular mechanics, molecular dynamics and quantum mechanical calculations.

In Coimbra, at CEMDRX, targets for structural studies include aminoacetic acids and their N-methylated derivatives having unusual electric properties ^[6,7]; chiral compounds and catalysts ^[6]; molecular rotors exhibiting ferroelastic behaviour ^[6]; Langmuir-Blodgett films related to kinetic reactions in biological membranes, molecular electronics and optical data storage ^[6]; five-membered heterocyclic compounds with potential anti-tumor and anti-leukemic activity and steroidal anticancer drugs ^[6].

References

[1] Technical University of Lisbon, Instituto Superior Técnico, Centro de Química Estrutural, M. Teresa Duarte (teresa.duarte@ist.utl.pt), M. Fátima M. Piedade (mdpiedade@fc.ul.pt), João Ferreira da Silva (joao.luis@ist.utl.pt), Adelino L. M. Galvão (adelino@ist.utl.pt), M. João Ferreira (mjoao.ferreira@netcabo.pt). [2] Instituto Tecnológico e Nuclear, Sacavém, Dept. de Química, Isabel C. Santos (icsantos@itn.pt), Dulce Belo (dbelo@itn.pt), Sandra Rabaça (sandrar@itn.pt).
[3] New University of Lisbon, ITQB – Instituto de Tecnologia Química e Biológica, Isabel Bento (bento@itqb.unl.pt), Pedro M. Matias (matias@itqb.unl.pt). [4] University of Porto, IBMC - Instituto de Biologia Molecular e Celular and ICBAS - Instituto de Ciências Biomédicas de Abel Salazar, Ana M. Damas (amdamas@ibmc.up.pt) and Luis Gales (lgales@ibmc.up.pt).
[5] University of Aveiro, Dept. de Química, Vítor Félix, (vfelix@dq.ua.pt).
[6] University of Coimbra, Physics Dept., CEMDRX, Margarida Costa (guida@pollux.fi s.uc.pt), Maria José Almeida (ze@pollux.fi s.uc.pt), José António Paixão (jap@pollux.fis.uc.pt), Lourdes Andrade (lourdes@pollux.fi s.uc.pt), Ana Matos Beja (ana@pollux.fi s.uc.pt), Manuela Ramos Silva (manuela@pollux.fi s.uc.pt).
[7] University of Minho, Physics Dept., Etelvina Matos Gomes (emg@fi sica.uminho.pt).

Protein crystallography: At ICBAS and IBMC [1] the molecular mechanisms underlying amyloidosis of transthyretin (TTR) is being studied. The current focus is on human transthyretin variants and transthyretin amyloid fibrils and the design of amyloid inhibitors and disrupters, on fasciolin, a small antigen secreted by the parasite Fasciola hepatica, and on other proteins including enolase, glutamine synthetase, biliverdin reductase and thrombin.

The Macromolecular Crystallography Laboratory at ITQB (Instituto de Tecnologia Química e Biológica) [2] has contributed to the understanding of 3D-structures of metalloproteins involved in electron transfer processes, including multiheme cytochromes, iron-sulfur and iron storage proteins. Recent projects involve structural studies of proteins related to cell adhesion during inflammatory processes in humans, a ribonuclease involved with the degradation of mRNAs, a lactase required for the assembly of the Bacillus subtilis endospore coat, complexes of β-cinnamomin, an elicitin from a phytopathogenic fungus, a fish osteocalcin, and some enzymes involved in the synthesis of polysaccharides. Collaborations with the Schering AG Berlin pharmaceutical company have supported the study of the androgen receptor ligand binding domain and a double mutant of this receptor in complex with a synthetic agonist. The structural characterization of catecol -O- methyltransferase with novel inhibitors that have potential use in Parkinson’s Disease therapy has been studied in collaboration with the Portuguese pharmaceutical company BIAL.
Many Biochemistry/Biology groups at ITQB are working with certain pharmacologically important protein membranes and the crystallography group has recently begun efforts to crystallize them.

The Protein Crystallography group at REQUIMTE (REde de QUÍMica e TEcnologia), Universidade Nova de Lisboa (UNL) ^[3], studies metalloproteins and proteins involved in electron-transfer processes. Targets include molybdopterin enzymes, xanthine oxidase-related enzymes, nitrate reductases and formate dehydrogenases, cytochrome c peroxidases, a membrane-bound multi-heme nitrite reductase, a sixteen-heme cytochrome, non-heme Fe/S proteins (e.g., superoxide reductase, a protein responsible for the scavenging of superoxide radicals in the cell), and several components of the “cellulosome”, a supramolecular assembly present in microorganisms that efficiently convert cellulose and its monomers to ethanol. Initial results include the first structures of the type I cohesin-dockerin complex and of several carbohydrate-binding modules (CBM). Also seen on the cover - protein published in Structure, 10, 1261-1272 (2002).

References

[1] University of Porto, IBMC - Instituto de Biologia Molecular e Celular and ICBAS - Instituto de Ciências Biomédicas de Abel Salazar, Ana M. Damas (amdamas@ibmc.up.pt) and Luis Gales (lgales@ibmc.up.pt), Pedro J. B. Pereira (ppereira@ibmc.up.pt).
[2] New University of Lisbon, ITQB – Instituto de Tecnologia Química e Biológica, M. Arménia Carrondo (carrondo@itqb.unl.pt), Pedro M. Matias (matias@itqb.unl.pt), Carlos Frazão (frazao@itqb.unl.pt), Margarida Archer (archer@itqb.unl.pt), Peter F. Lindley (lindley@itqb.unl.pt), Isabel Bento (bento@itqb.unl.pt), Francisco Enguita (fenguita@itqb.unl.pt), Maria Luísa Rodrigues (mariar@itqb.unl.pt), Colin McVey (mcveyo@itqb.unl.pt), Daniele di Sanctis (sanctis@itqb.unl.pt), Meike Stelter (meike@itqb.unl.pt), Célia Romão (cmromao@itqb.unl.pt), Tiago Bandeiras (tiagob@itqb.unl.pt).
[3] New University of Lisbon, Faculdade de Ciências e Tecnologia, REQUIMTE/CQFB, Maria João Romão(mromao@dq.fct.unl.pt), Ana Luisa Carvalho (alcarvalho@dq.fct.unl.pt), José Trincão (trincao@dq.fct.unl.pt), Shabir Najmudin (shabir@dq.fct.unl.pt).

Teaching: Crystallography was originally taught as an independent discipline in the Geology Departments of Porto and Lisbon Universities. However, since the fifties, it has been taught along with Mineralogy and Solid State Physics and Chemistry in most Portuguese universities. Two decades ago Crystallography began to be taught at Universidade Nova de Lisboa as an independent and basic discipline within a course on Materials Science and Engineering along with Crystal Chemistry under the guidance of Maria Ondina Figueiredo.

Courses, meetings and conferences: During the past 25 years, ten international conferences covering a broad range of crystallographic topics, including synchrotron, X-ray, and neutron radiation, XAFS, SEXAFS techniques and their application to electron density studies and materials research, and biological and medical science have been organized and conducted in Portugal, including NATO Advanced Study Institutes, a Sagamore conference and the 1997 European Crystallographic Meeting (ECM 17).

The first BioCrys-Course on ‘Fundamentals of Modern Methods in Biocrystallography’ at the Instituto de Tecnologia Química e Biológica in Oeiras, in October, 2002, was organized by Maria Arménia Carrondo and Thomas Schneider. The course covered fundamental theoretical concepts of macromolecular crystallography and was geared toward scientists in the early stage of their crystallographic career. This is particularly important due to the rapid development of the field and the fact that many young researchers no longer receive any formal education in crystallography.
A second and third edition of this course took place at ITQB, Oeiras, in November 2004 and October, 2006.

Involvement with European Crystallography Meetings (ECMs): Portugal has been involved with the organization of several ECMs by participating in the Programme Committee of ECM 16 (Sweden), ECM 18 (Czech Republic), and ECM 19 (France).

However the most significant contribution to crystallography was the organization of ECM 17, which took place in Lisbon in 1997. This was a joint effort involving the entire senior Portuguese crystallographic community along with many students. Maria-Ondina Figueiredo chaired the Scientific Committee and Maria Arménia Carrondo chaired the Organizing Committee. This meeting hosted over 900 participants from 47 different countries. The scientific programme included 3 plenary lectures, 12 session lectures, 36 mycrosymposia on macromolecules; small and medium sized molecules; minerals, materials, inorganic compounds; techniques and instrumentation; and multidisciplinary studies.

A satellite meeting on ‘Validation and refinement of macromolecular structures’ took place just after the ECM 17. It was organized by Ana M. Damas at IBMC-Porto and over 100 participants from 17 different countries attended the meeting.

Involvement with the European Crystallographic Committee (ECC), European Crystallographic Association (ECA) and the IUCr: José Lima de Faria represented Portugal on the ECC since its founding in 1973. When the ECA was created during ECM17 in Lisbon, Maria Arménia Carrondo became an Officer of the Executive Committee. Maria Teresa Duarte was elected ECA treasurer in 2000 at ECM19 and still holds this position. Presently Ana Margarida Damas and Margarida Archer are the Portuguese representatives on the ECA Council.

IUCr involvement also started with José Lima de Faria as the Portuguese representative to the General Assembly until 1996 when he was followed by Maria Arménia Carrondo who was elected in 1999 to the IUCr Executive Committee (August 1999 - August 2005). Since 1999, Margarida Costa, Ana Margarida Damas and Maria Teresa Duarte have represented Portugal at the IUCr General Assemblies. Maria Arménia Carrondo was designated Chair of the IUCr Sub- Commission on the Union calendar (August 2002-August 2005). She was a member of the European Crystallographic Association Committee for the Max-Perutz Prize in 2006.

Membership in the European Synchrotron Radiation Facility (ESRF): In 2004 the ESRF in Grenoble celebrated its 10th year of user operation. Although not among one of the twelve European contracting countries, Portugal was the first to join as an Associate Member in 1998. Portuguese scientists have used the ESRF for projects in the areas of protein crystallography, chemistry, physics, and materials and environmental sciences. Portuguese scientists have been involved in the ESRF Council and in the Scientific Advisory Committee as well as sitting on Evaluation Panels for projects in these research fields.

Portugal became an Associate Member of the Partnership for Structural Biology (PSB) just after it was founded in November 2002. The Partnership’s goal is to make use of the structural biology expertise and techniques available at the Grenoble site to build an integrated resource for structural genomics and proteomics in Europe that will focus on proteins with medical interest. ESRF, the European Molecular Biology Laboratory (EMBL), the Institut Laue-Langevin (ILL) and the Institute of Structural Biology (IBS) were the local founding members of the PSB. A number of pharmaceutical companies have also joined the PSB as Associate Members.

Maria Ondina Figueiredo, Margarida Costa, Ana Margarida Damas, Maria Teresa Duarte, Maria Arménia Carrondo